Findings from our laboratory have shown that asymptomatic sexually transmitted infections (STIs) have a significant effect on foreskin immunity, by increasing the density of HIV target cells in the foreskin and altering inflammatory markers in the tissue. Of particular importance, CCL27 transcript and protein were found to be significantly higher in the inner foreskin relative to the outer tissue. We hypothesized that CCL27, a skin-homing chemokine, might have an effect on recruiting HIV target cells to the foreskin epidermis, bringing target cells closer to where they might interact with HIV upon exposure.
Inner foreskin tissue explants were cultured in either media alone or in the presence of TNFα (100ng/ml) or CCL27 (400ng/ml) for 48 hours. Tissue was embedded and frozen in OCT, sectioned and stained for HIV target cells (CD3+CD4+). A Delta Vision imaging system was used to acquire fluorescent images of the cells. Cell density was then calculated using Integrative Data Language (IDL), accounting for the size of the epidermis.
We observed an increase in the density of CD3+CD4+ T cells in the epithelium of the inner foreskin that was stimulated with CCL27. The data showed a 2- to 3-fold (q<0.001) increase in CD3+CD4+ T cell numbers in the epithelium after stimulation with TNFα (from 60 cells/mm2 to 138 cells/mm2) and CCL27 (from 60 cells/mm2 to 147 cells/mm2) compared to the unstimulated samples.
In conclusion, exogenous stimulation of foreskin tissue with CCL27 was shown to significantly increase the population of CD3+CD4+ T cells in the inner foreskin. It is suggested that this increase is due to the migration of CD3+CD+ T cells from deeper layers of the tissue to the epithelium. Interestingly, CCR10 is the cognate receptor for CCL27 that is expressed on T helper 22 (Th22) cells. Th22 cells express CCR5, making them a possible target for HIV infection. Future work can explore how the interaction of CCL27 and Th22 cells in the foreskin affect HIV susceptibility in the male genital tract.